Synthetic Biology of Sclareol: From the Plant Biosynthetic Pathway to Engineered Microbial and Photosynthetic Chassis.

Sclareol is a highly valued bicyclic diterpene widely used as a precursor for the fragrance ambroxide and has also attracted interest as a bioactive natural product. Traditional production relies heavily on plant extraction, primarily from Salvia sclarea, an approach constrained by environmental variability, long cultivation cycles, and costly downstream purification. To overcome these supply bottlenecks, synthetic biology-enabled biomanufacturing has emerged as a sustainable and scalable alternative. Recent advances in synthetic biology and metabolic engineering have enabled the elucidation and reconstruction of the sclareol biosynthetic pathway in heterologous hosts. This review summarizes current knowledge of sclareol biosynthesis, highlights representative engineering strategies for its production in microbial cell factories, while briefly introducing emerging photosynthetic and plant-based platforms as complementary green production systems. Finally, we outline the current challenges and future perspectives for the industrial biomanufacturing of sclareol and other high-value terpenoids.